Fluid Bed Processor - GEA Pharma Systems

Fluid Bed ProcessorAeromatic-Fielder TechnologiesGEA Pharma Systems

GEA Pharma Systems is world leader in providingadvanced processing solutions for solid dosage forms tothe pharmaceutical industry. Based on a dedication toresearch and durable quality, GEA Pharma Systemsoffers a wide range of solutions, from individual piecesof equipment to complete integrated plants, by unitingthe state-of-the-art technologies of Aeromatic, Buck,Collette, Courtoy, Fielder, Lyophil, Nica and Niro.

Product Know-HowProcess Expertise•For more than forty years, Aeromatic-Fielder has supplied advancedsolids processing plants for blending, granulating, drying, pelletizingand coating to the pharmaceutical industry. This includes smallcapacity systems designed for R & D as well as industrial size plantsfor batch production of pharmaceutical compounds under cGMPconditions.Our plant and process expertise is based on experience and R & D. With plants installedaround the world and literally thousands of tests performed, we have established a solidbase of expertise related to the needs of the pharmaceutical manufacturing industry.Delivering the Right SolutionsEvery Aeromatic-Fielder plant begins with thecustomer’s desire to create a product that willsucceed in the market. In Aeromatic-Fielder, thecustomer finds a partner who will assist him to meetthat goal. Our expertise includes technologies forprocessing Active Pharmaceutical Ingredients using,Blending, Granulating, Drying, Pelletizing andCoating.Plants Customised for SuccessEvery pharmaceutical plant and system fromAeromatic-Fielder is a unique union of proventechnology and individual solutions. Based onstandard components, we supply plants for cGMPproduction configured to meet the customer’sspecific requirements.A Partnership in Every PerspectiveWorking with Aeromatic-Fielder means entering asolid partnership every step of the way, from processtesting and design to specification of the softwarecontrolling your new plant. And our comprehensiveafter sales program ensures that your return oninvestment is optimised throughout the lifetimeof the plant.Safety and the environmentFor full compliance with national, local and in-houseregulations, Aeromatic-Fielder offers a range ofemission control options including solvent recoverysystems, outlet filters and full containment plants.Equipment can be supplied to meet explosion-proofand pressure shock standards as required.3

• Drying • Granulating • Pelletizing • CoatingProcessTechnologies•For maximum process flexibility, Aeromatic-Fielder cansupply a single Fluid Bed unit or Multi-Processor systemwith interchangeable modules.DryingWarm air is blown through a perforated distributor to rapidly and gentlydry materials until the required residual moisture content is reached.Moisture evaporated from the product is exhausted with the drying air.DryingSpecial featuresSelection of air distributorsShort process timeTop Spray GranulatorThe top spray granulator agglomerates finer particles into larger, freeflowing granulates in a one-pot process. Ingredients are mixed and preheatedby an upward flow of heated air. Granulation occurs by sprayingliquid into the fluidized powder. The granules are subsequently dried withheated air. The top spray granulator can also be used for top spray coating,layering from liquids, and instantizing.Top SprayGranulatorSpecial featuresOne pot processSelection of air distributorsSpray Dryer GranulatorThe spray dryer granulator transforms suspensions or solutions into dry,free-flowing, dustless granules. A suspension or solution of the substanceto be dried is sprayed onto warm air, simultaneously drying andagglomerating the product. Batch or continuous discharge is available – inthe continuous mode, the product is discharged at a controlled rate tomaintain an optimum bed heightSpecial featuresCompact unitEasy scale-upBatch or continuous dischargeSprayDryerGranulator4

Built-in VersatilityPrecision-GranulatorA rotating high velocity air stream is established in the centralagglomeration tube. Particles are picked up at the base of the tubeand accelerated by the air stream. The particles come into contactwith liquid droplets produced from the spray nozzle at the base ofthe tube \ the relative velocity of air, liquid droplets and particlesare high so wetting is efficient and drying begins almostimmediately. Most of the feed material is in the outer “holdingarea”, where the gas velocity is very low. Attrition is greatlyreduced. The gas humidity is also low in the holding area so thematerial is dry not sticky. Individual particles may make repeatedcycles (typically from 10 to 1,000) through the tube, allowing verylarge agglomerates to be built up.PrecisionGranulatorPrecision-CoaterUsed for smaller particles, such as powders, granules, seeds, crystals,pellets, and small tablets. The product is coated and partially dried bybeing blown upward through a central column with atomized liquidand drying air. The material falls into the outer part of the containerwhere heated air completes the drying process. On reaching the airdistributor at the base of the module, the product flows again intothe central column for further coating. This process continues untilthe specified degree of coating is obtained.PrecisionCoaterSpecial featuresHigh spray rates for short processesHighly controlled product movementMinimal agglomeration or granulation5

Batch FluidTechnology•Using proven standard components, Aeromatic-Fielder can supplyboth simplicity and flexibility in plant design. User-selected processmodules, filters, control systems and air preparation units combinein a system to meet process requirements exactly. This modularapproach ensures that qualification and validation procedures arekept to a minimum.Through-the-wall installationBy positioning the support column at the back of thefluid bed, a through-the-wall installation is achievedwhich ensures that all the auxiliary equipment ishoused outside the process room. This greatlysimplifies compliance with GMP guidelines.Solvent emission controlA range of open- and closed-cycle systems forremoving or recovering organic solvents is available.Options include condensation, adsorption, thermaloxidation and wet scrubbing.Externalbag fitterNormally used inconjunction withthe particleretainer tocollect dust fromthe fluid bed incoatingapplications.Spraying systemsNozzles, pumps and liquid preparation units aresupplied according to process needs.Product dischargeFor automatic product discharge, pneumaticconveying or gravity-based systems are available foruse with the Non-Sifting Gill Plate air distributortechnology.Open CycleDesignInlet air preparation unitInlet air is treated using a series of filters andconditioning units according to the sensitivity of theprocess and the ambient climatic conditions. Optionsrange from the basic minimum, consisting of a prefilter,heater and final filter, to full air-conditioning toprovide consistent processing conditions all yearround. Condensers are used for dehumidifying inmost applications, but for hygroscopic oreffervescent products which require a very low dewpoint, additional adsorption devices can be installed.Humidification is achieved by an injection of steam.Quickclosing valveHEPA filter6

Optimized DesignsProcess filtersIn granulation, drying, and most pelletizingapplications, a process filter is used to trapQuick closingvalvePolice filtersSuction fanSilencermall particles, which are returned to the bedwhen the filter is cleaned. In coatingapplications, fine particles usually need to beremoved. Fluid beds that are used for morethan one type of process can be suppliedwith interchangeable process filters.11 Single shaker bag filterA simple, basic filter with a single bag,which is cleaned by shaking. Fluidizationstops during filter cleaning.2 Multi shaker bag filter2This filter is divided into two or moresections, with a separate filter bag in eachPre-filterPre-heaterone. Bags are cleaned individually byshaking the filter, while fluidizationcontinues in the other sections, for fasterand more efficient production.Humidifier3 Blow-back filterThere are multiple filter bag sections in thisdesign. Cleaning takes place one bag at atime, so that a large proportion of the filteris always available for continuousfluidization.34 Cartridge filterStainless steel filter cartridges are cleanedFilterHeater (faceand by-pass)Cooler/condenserone at a time, so that a large proportion ofthe filter is always available for continuousfluidization. Unlike bag filters, this systemcan be cleaned-in-place.45 Particle retainerUsed for coating applications, this designretains the coarser particles and returnsthem to the process, removing the dust to anexternal filter unit.57

Understanding& ControllingYour Process•For optimum compatibility with existing plant control strategies,fluid bed systems are available with a choice of manual or FDAcompliant automated controls. Programmable logic controller(PLC) and PC-based options offer a wide range of recipe handling,data acquisition and network communication functions.SynTQ PAT data analysis andmodelling platformMaterialsinformationPAT dataProcessoptimisationMultivariateanalysisProcessengineeringmodelsControlsThe PLC front panel key-pad and built-in monitorare used for recipe programming and real-timeprocess MIMIC display.For optimum compatibility with existing plantcontrol strategies, fluid bed systems are availablewith a choice of manual or FDA compliantautomated controls. Programmable logic controller(PLC) and PC-based options offer a wide range ofrecipe handling, data acquisition and networkcommunication functions.Drying curve monitored byNDC Pharmaveiw NIRmoisture measurement systemMonitoring coating conditionsGPS real time process humidity model(RTPD) (above) to navigate the pychometricchart (belowMonitoring of coat growthusing Zeiss Corona NIR8

In processs measurement position Clean and calibrate position CIP position at end of processGEA Pharma Systems integrate processengineering and PAT to provide ProcessIntelligenceThe FDA’s PAT (process analytical technologies)initiative has enabled GPS Pharma Systems tocombine its equipment design skills and processengineering know–how in order to integrate online(PAT) analysers into its process systems in a waywhich can provide real insight into the operation ofthe process and help customers achieve key productquality target .The goal of the PAT initiative is to ensure thatpharmaceutical products are manufactured usingprocesses which are understood and monitored sothat the key quality characteristics of the productscan be actively controlled.Combining process monitoring using onlineanalysers, together with solid process engineeringprinciples and advanced process modellingtechniques will enable processes to be activelycontrolled in order to compensate for minor inputvariations (eg. raw materials) so that thespecifications for the final product will be closer tothe ideal target.Using process models to identify the processconditions that highlite products which performbest in subsequent processes will enable the wholeproduction process to be targeted towards theperformance of the final dose rather than justoptimising each unit operation individually. GPSPharma Systems wide scope gives it a uniqueperspective on the complete process.Lighthouse ProbeTechnologyGEA Pharma Systems (GPS) has joinedforces with J&M GmbH to create acompact and cleanable in-process opticalprobe for use in powder processingequipment.The result is the novel Lighthouse Probe, whichcan be used with a range of spectroscopictechniques, including NIR and UV/vis, to overcomethe traditional problem of product sticking toobservation windows.The probe is compact and easy to install and makesit possible to take a reliable in process measurementof quality critical product characteristics including:• Material and active content identification• Active content uniformity during high shearblending operations• Moisture content and end-point duringdrying processes• Coat growth during coating processesOptical methods such as UV/Vis or NIRspectroscopy can be very powerful tools foranalysing a range of product characteristics, but inprocesses involving wet and sticky powders it isnecessary to ensure that the system has a clear viewof the product. Conventional windows used inprocess equipment such as fluid bed systems or highshear granulators, have always suffered from therisk of window fouling. The new GPS & J&MLighthouse Probe has overcome this problem.9

Sizes &Meeting EveryRequirement •CapacitiesStandard modules configured into tailor-made plants.The philosophy behind the design is that a combination ofstandardised modules are built together in order to meet therequirement for a specific duty. Therefore, dryers of equal capacitymay be completely different with respect to design, configurationand physical size.To meet the high requirements of the pharmaceutical industry,Aeromatic-Fielder has a series of fluid bed systems suitable forformulation, process development, production of clinical materialthrough to full-scale production.Production capacities150 300 400 400 600 800 1200 1800 2400 3000(Size 3) (Size 4) (Size 5) (Size 5) K3 (Size 6) (Size 6) K3 (Size 7) (Size 8) (Size 9) (Size 10)Typical workingcapacity 30 to 100 L 60 to 200 L 90 to 300 L 90 to 400 L 120 to 400 L 120 to 600 L 240 to 800 L 360 to 1200 L 480 to 1600 L 600 to 2000 LTypical batchcapacity(average product density 0.5kg/l) 15 to 50 kg 30 to 100 kg 45 to 150 kg 60 to 200 kg 60 to 200 kg 90 to 300 kg 120 to 400 kg 180 to 600 kg 240 - 800 kgs 320 to 1200 kgMaximumworking volume 125 L 225 L 355 L 450 L 600 L 650 L 900 L 1350 L 1800 L 2250 LValues are process and product specific and may vary from those shown above.10

IntegrationOptimumProcess Efficiency•Current Good Manufacturing Practices increasingly require thatproduct is fully contained during processing to protect operatorsand environment. Integrated process systems not only offercontainment but improved productivity through automation,increased yield and efficient cleaning procedures.System integrationGEA Pharma Systems specialises in the design andmanufacture of fluid bed and high-shear granulationtechnology and is uniquely qualified to providestate-of-the-art integrated high shear mixergranulatorand fluid bed drying technology. Drawingon its world-class expertise, GPS Pharma Systemsoffers fully integrated turnkey installations. Theservice includes: design, installation assistance,commissioning, process validation, as well astraining, and technical support. Installation,operation qualification and documentation arecarried out according to FDA/GAMP guidelines.Integration by designAeromatic-Fielder’s entire range of processequipment is designed with system integration inmind. A modular approach allows customers toselect standard process modules to suit projectneeds. Fluid bed dryers and coaters can be combinedwith top-drive and bottom-drive high shear mixergranulators,wet and dry milling facilities, producthandling systems, binder and coating preparationunits, filtration units, all designed for fullyintegrated systems. Safety, containment, productflow and building requirements are in-built for fullintegration for optimum process efficiency11

DesignCleanability &Maintenance •Process optimisation depends on efficient, effectivecleaning. Automation of the cleaning process ensuresrepeatability, allows validation and minimises down-time.In recognition of the fundamental role played in today’sadvanced powder processing industry by automated cleanin-placeprocedures Aeromatic-Fielder has developed aunique approach to CIP.WIP and CIPAll process plant can be supplied with a basic washin-place(WIP) system or with fully automatedcleaning-in-place system. CIP options for the fluid bedprocessor include process filters that do not have to beremoved for cleaning.CIP Kitchen12

Safety &the environment•ContinuousImprovementFor full compliance with national, local and in-house regulations,GPS Pharma Systems offers a range of emission control optionsincluding solvent recovery systems, outlet filters and fullcontainment plants. Equipment can be supplied to meetexplosion-proof and pressure shock standards as required.Improved safety for integrated granulationand drying suitesExtensive safety testing confirms pressureenhancement effects and identifies safe designlimits for integrated systems GPS Pharma Systemsin conjunction with the FSA, the safety specialistcentre in Germany, have carried out an extensive testprogramme involving over 100 test explosions. Thisresearch has shown conclusively that should anexplosion occur during the transfer operation in anintegrated system where a granulator is connecteddirectly to a fluid bed dryer without an explosionisolation valve, the secondary explosion pressures inthe granulator can be significantly higher than inthe fluid bed. These tests have enabled GPS PharmaSystems to gain full EC type approval for a range ofpressure shock resistant integrated systems and 16-bar pressure shock resistant high shear granulators.Safety when using organic solventsThe tests were carried out with hybrid mixtures thatbehave in the same way as pharmaceutical productscontaining organic solvents and showed that the finalexplosion pressure in the granulator is dependent onthe volumes of the two vessels and that the lengthand diameter of the interconnecting duct is critical inensuring that the pressure remains within safe limits.The tests showed that where the fluid bed is designedin accordance with VDI 2263 part 5 (i.e.: for a 10-barexplosion pressure, which the standard considers tobe adequate for all pharmaceutical powders andorganic solvent combinations), then the granulatormust be able to withstand an over pressure of at least16 bar to provide a range of transfer ductconfigurations which are both practical and safe.Where the fluid bed is required to handle materialswith explosion pressures greater than 10 bar (e.g.:metal powders) - and hence is designed outside ofthe VDI standard - or where the configuration of theinterconnecting duct is outside the safe designparameters, then either the granulator must bedesigned to a higher pressure shock resistance or ahygienic fast acting valve, or some other form ofprotection, is essential. The test program showedthat the pressure enhancement effects are caused bythe difference in the propagation speed between thepressure wave and the flame front. The worst casesare when the pressure in the granulator is able torise significantly before the flame can reach it andignite the pre-compressed material. For the range oftransfer duct configurations to be used with the 16-bar granulator design, the presence of bends andobstructions such as mills was not seen to affect theincrease in pressure.For plant processing powders, or mixtures that arenot flammable at the time of transfer between thegranulator and the fluid bed, then the risk ofexplosion is eliminated and hence a wider range oftransfer duct designs can be used safely. Thisextensive research program has significantlyadvanced the state of the art in safety technology forpharmaceutical plants and confirms GPS PharmaSystems’ commitment to introducing new productswhich are based on sound research and developmentusing solid process know how and understanding.10 bar PSRdesign (norelief ductneccessary)Explosionsuppressionsystem (no reliefduct neccessary)2 bar PSRdesign withexplosionrelief duct13

The CompletePartnership •Working with you…Entering a partnership with Aeromatic-Fielder means entering a partnership that doesnot end until you are completely satisfied. From the moment you have specified youruser requirements and until the plant has been put into service and has beenqualified, our trained staff stays with you at every step of the process, working inclose co-operation with your own staff creating the components and systems that willresult in a finished plant.CustomerresponsibiltyUser RequirementsClient VerificationProcess QualificationFunctional SpecificationAeromatic-Fielder /Client VerificationOperational QualificationJoint tasksSoftwaredesignHardwaredesignMechanicaldesignInstallation QualificationMechanical equipment buildFAT testingAeromatic-FielderresponsibiltyHardware manufacturingSoftware ConfigurationIntegrated testingBench testing…Every Step of the WayBased on years of experience, equipment qualification will be carried out according toan agreed plan using documents prepared by Aeromatic-Fielder.Our engineers will contribute to a successful qualification of the equipment in closeco-operation with your validation staff.14

Servicefor Life•Project ManagementThe expertise of the Aeromatic-Fielder engineeringteam is available to help customers find theoptimum solution for their individual processingneeds. The company assists with single phases of aproject, or takes full responsibility for design andinstallation of a complete turnkey plant.TrainingOperators of Aeromatic-Fielder equipment canundergo training to help them maximise efficiency,either at the time of installation or periodically asrequired.After SalesRegular maintenance is essential to ensureequipment operates to maximum efficiency. Fullytrained engineers can carry out on-site servicing andcalibration of equipment, either as part of a plannedmaintenance programme or in response to customerneed. Replacement parts can be supplied from stockor manufactured to order.To avoid the expense of equipment replacementAeromatic-Fielder can upgrade existing systems andplant to meet different operational parameters, tocomply with changing regulations, or to modify foruse at another location.15

www.geapharmasystems.comCentral Know-How on a Global ScaleBased on a strong commitment toresearch and development,pharmaceutical technology centres inBelgium, Denmark, Switzerland, the UK,Singapore, and USA provide globaltechnical support and know-how to thepharmaceutical industry. These centresof excellence give customers access to a range of test facilities and expertteams with technical and process know-how. Our teams work closely withour customers to optimise processes and evaluate their products, enablingthem to achieve their process and production goals.Contracting Profitable ExperienceA world leader in supplyingpharmaceutical equipment, GEA PharmaSystems offers manufacturers all overthe world the opportunity to enter into aprofitable partnership for developmentand contract. GPS combine advanced inhousetechnology with a thoroughunderstanding of the pharmaceutical industry to help customers maximizetheir development results.© GEA Pharma Systems 2008 Specifications subject to change without notice All trademarks recognizedGEA Pharma SystemsAeromatic-FielderGEA Pharma Systems AGPO Box 112, Hauptstrasse 145CH-4416 Bubendorf, SwitzerlandTel: (CH) +41 61 936 36 36, (UK) +44 23 8026 7131aeromatic-fielder@geapharmasystems.com